Pulsatility Protects the Endothelial Function during Extracorporeal Membrane Oxygenation

Background: Pulsatile flow has been proved to protect vital organ function and microcirculation during extracorporeal membrane oxygenation (ECMO). Studies revealed that pulsatile shear stress plays a vital role in the microcirculatory function and integrity. The objective of this study was to investigate how pulsatility affects wall shear stress and microcirculation during ECMO. Methods: Using the i-Cor system, we compared the effects of pulstile or non-pulsatile flows in a canine ECMO model, with hemodynamic parameters and peak wall shear stress (PWSS) calculated. Serum concentrations of syndecan-1 and heparan sulfate were measured at different time points during ECMO. Pulstile shear stress experiments were also validated in endothelial cells exposed to different magnitude of pulsatility, with cell viability, the expressions of syndecan-1 and endothelial-to-mesenchymal tranformation (EndMT) markers analyzed. Results: The pulsatile flow generated more surplus hemodynamic energy and preserved higher PWSS during ECMO. Serum concentrations of syndecan-1 and heparan sulfate were both negatively correlated with PWSS, and significantly lower levels were observed in the pulsatile group. In addition, non-pulsatility triggered EndMT, with EndMT related genes up-regulated, and endothelial cells exposed to low pulsatility had the lowest possibility of EndMT. Conclusion: The maintenance of the PWSS by pulsatility during ECMO contributes to the beneficial effects on glycocalyx integrity and microcirculatory function. Moreover, pulsatility prevents EndMT in endothelial cells, and low pulsatility exhibits the best protective effects. The augmentation of pulsatility may be a future direction to improve the clinical outcome in ECMO. Funding: This study did not receive specific fundings. Declaration of Interest: All authors declare no conflict of interest. Ethical Approval: Ethical approval was obtained from the Institutional Animal Care and Use Committee of Sun Yat-sen Memorial Hospital (Reference No. SYSUIACUC-2020-B0402). The experimental setting was established in accordance with the Guide for the Care and Use of Laboratory Animals by the National Institute of Health (NIH) of the United States (revised in 1985).